Related Experiment Video
Updated: Dec 17, 2025
08:32
Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
Published on: March 16, 2017
13.2K
The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway
V Kapil1, R S Khambata1, D A Jones1
1William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, United Kingdom (V.K., R.S.K., D.A.J., K.R., C.P., G.M., A.A.) and Department of Chemistry, Sonoma State University, Rohnert Park, California (J.M.F.).
Pharmacological Reviews
|June 25, 2020
Summary
Nitrite and nitrate, once thought inactive, are now known to be crucial storage forms of nitric oxide. This pathway offers therapeutic potential for conditions like hypertension and ischemia/reperfusion injury.
Area of Science:
- Physiology and Pharmacology
- Cardiovascular Research
- Nitric Oxide Metabolism
Background:
- Nitric oxide (NO) has established roles in blood flow, neurotransmission, and immunity.
- Previously, its metabolites nitrite and nitrate were considered inactive.
- Recent research reveals nitrite and nitrate as vital NO precursors.
Purpose of the Study:
- To review the bioactivation pathways of nitrate and nitrite in vivo.
- To discuss their functional effects in preclinical and clinical settings.
- To explore therapeutic potential in NO-deficient diseases.
Main Methods:
- Literature review of preclinical and clinical studies.
- Analysis of molecular pathways for nitrate and nitrite reduction.
- Examination of functional outcomes and mechanisms of action.
Main Results:
- Nitrite acts as an NO reservoir, releasing NO under specific conditions via nitrite reductases.
- Nitrite reduction yields beneficial effects: vasodilation, blood pressure reduction, and cytoprotection against ischemia/reperfusion.
- Nitrate can be sequentially reduced to nitrite and then NO, also lowering blood pressure, confirmed in hypertensive patients.
Conclusions:
- The nitrate-nitrite-nitric oxide pathway is a significant noncanonical route for NO generation.
- This pathway demonstrates therapeutic promise for cardiovascular diseases and other conditions.
- Understanding and targeting this pathway offers new avenues for treatment.
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